Showing papers by "Paula Ghaneh published in 2007"

Meta-Analyses of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer

Abstract: Purpose There are a large number of randomized controlled trials involving chemotherapy in the management of advanced pancreatic cancer. Several chemotherapeutic agents, either alone or in combination with other chemotherapy or novel agents, have been used. The aim of these meta-analyses was to examine the different therapeutic approaches, and the comparisons examined were as follows: chemotherapy versus best supportive care; fluorouracil (FU) versus FU combination chemotherapy; gemcitabine versus FU; and gemcitabine versus gemcitabine combination chemotherapy. Methods Relevant trials were identified by searching databases, trial registers, and conference proceedings. The primary end point was overall survival. Results One hundred thirteen randomized controlled trials were identified, of which 51 trials involving 9,970 patients met the inclusion criteria. Chemotherapy improved survival compared with best supportive care (hazard ratio [HR] = 0.64; 95% CI, 0.42 to 0.98). FU-based combination chemotherapy di...

Branch-duct intraductal papillary mucinous neoplasms of the pancreas : to operate or not to operate? Commentary

Abstract: Background: Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are reported to be less aggressive than the main-duct type. Hence, less aggressive treatment has been proposed for the former. Aim: To evaluate the effectiveness of a follow-up protocol for BD-IPMNs. Design: Prospective study. Setting: An academic tertiary referral centre. Patients: From 2000 to 2003, 109 patients with BD-IPMNs underwent trans-abdominal ultrasound and magnetic resonance cholangiopancreatography with secretin. Patients who presented malignancy-related parameters (size >3.5 cm, nodules, thick walls, carbohydrate antigen 19.9 level >25 U/l, recent-onset or worsened diabetes) and/or complained of symptoms were submitted to surgery (arm A). All asymptomatic patients without suspicion of malignancy were followed up according to a 6-month clinical-radiological protocol (arm B). Main outcome measures: The effectiveness of conservative management of BD-IPMNs. Results: 20 (18.3%) patients underwent surgery (arm A); pathological diagnosis of BD-IPMNs was always confirmed. 89 (81.7%) patients were followed up for a median of 32 months (arm B); of these, 57 (64%) patients had multifocal disease. After a mean follow-up of 18.2 months, 5 (5.6%) patients showed an increase in lesion size and underwent surgery. The pathological diagnosis was branch-duct adenoma in three patients and borderline adenoma in two. Conclusions: Surgery is indicated in <20% of cases of BD-IPMNs, and, in the absence of malignancy-related parameters, careful non-operative management seems to be safe and effective in asymptomatic patients. Although observation for a longer time is needed to confirm these results, our findings support the guidelines recently recommended by the International Association of Pancreatology.

Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy

Abstract: There is no consensus on the management of locally advanced pancreatic cancer, with either chemotherapy or combined modality approaches being employed (Maheshwari and Moser, 2005). No published meta-analysis (Fung et al, 2003; Banu et al, 2005; Liang, 2005; Bria et al, 2006; Milella et al, 2006) has included randomised controlled trials employing radiation therapy. The aim of this systematic review was to compare the following: (i) chemoradiation followed by chemotherapy (combined modality therapy) vs best supportive care (ii) radiotherapy vs chemoradiation (iii) radiotherapy vs combined modality therapy (iv) chemotherapy vs combined modality therapy (v) 5FU-based combined modality treatment vs another-agent-based combined modality therapy. Relevant randomised controlled trials were identified by searching databases, trial registers and conference proceedings. The primary end point was overall survival and secondary end points were progression-free survival/time-to-progression, response rate and adverse events. Survival data were summarised using hazard ratio (HR) and response-rate/adverse-event data with relative risk. Eleven trials involving 794 patients met the inclusion criteria. Length of survival with chemoradiation was increased compared with radiotherapy alone (two trials, 168 patients, HR 0.69; 95% confidence interval (CI) 0.51–0.94), but chemoradiation followed by chemotherapy did not lead to a survival advantage over chemotherapy alone (two trials, 134 patients, HR 0.79; CI 0.32–1.95). Meta-analyses could not be performed for the other comparisons. A survival benefit was demonstrated for chemoradiation over radiotherapy alone. Chemoradiation followed by chemotherapy did not demonstrate any survival advantage over chemotherapy alone, but important clinical differences cannot be ruled out due to the wide CI.

A new approach to managing intraductal papillary mucinous pancreatic neoplasms

Abstract: Progress in the diagnosis and management plan for this pancreatic neoplasm A large prospective study by Salvia et al 1 published in this issue of Gut shows that a follow-up protocol for branch duct intraductal papillary mucinous neoplasms (IPMNs) appears feasible and safe ( see page 1086 ). IPMNs of the pancreas were originally described in a number of case reports and short series of patients in the early 1990s,2,3 and mucinous cystic neoplasms of the pancreas had been reported in the 1980s.4–6 In 1996 the World Health Organisation (WHO) revised the criteria for the pathological diagnosis of IPMN,7 thus allowing the differentiation of IPMN from other mucinous/cystic neoplasms of the pancreas. This meant that a number of “different” neoplasms could now come under the single diagnostic umbrella of IPMN (table 1). View this table: Table 1 Classification and characteristics of intraductal papillary mucinous neoplasms (IPMNs) The apparent incidence of IPMN has increased dramatically over the past 10–15 years and now represents up to 10–20% of the pancreatic resection workload of specialist units.8 This is due in part to improved imaging techniques, greater recognition of this clinicopathological entity and a larger number of asymptomatic patients undergoing cross-sectional imaging.9 Histologically, IPMNs progress along a pathway from adenoma to borderline IPMN with dysplasia to IPMN with carcinoma in situ and eventually to invasive carcinoma. It is not always possible to differentiate high-grade and low-grade lesions on imaging alone, and the time to progression is not known. The association of IPMNs (particularly the gastric type variant) with the precursor lesions of pancreatic ductal adenocarcinoma known as pancreatic intra-epithelial neoplasms (PanINs) or PanIN-like lesions may provide further information concerning their development.10,11 Molecular analysis may provide biomarkers of disease progression in the near future with further follow-up of patients with characterised lesions. The …

Comment on: Adjuvant Therapy in Pancreatic Cancer : A Critical Appraisal. Authors' reply

Abstract: In issue 67 (16) of Drugs, Drs Helmut Oettle and the use of ‘background’ therapies, and inadequate Peter Neuhaus[1] review the lexicon of significant attention to the details of radiotherapy administratrials undertaken for the study of adjuvant therapy tion and quality control. In an effort to address these following resection with curative intent for pancreconcerns, a subsequent publication of the data of this atic adenocarcinoma. Their approach is thorough trial, limited to only those patients strictly entered and careful, and has much to recommend it. In the into a 2 × 2 randomisation scheme of surgery, surend, however, they conclude that available recent gery plus chemoradiotherapy, surgery plus chemoevidence suggests that radiotherapy should no longtherapy, or surgery plus chemoradiotherapy and er be included in such therapy outside of research chemotherapy, was published.[4] However, as pointsettings. My reasons for disagreeing with this coned out elsewhere,[5,6] the results of this subset are clusion are summarised in table I and discussed in atypical. Surgery alone resulted in a survival of turn. 16.9 months, which is much longer than that seen with any other randomised trial utilising a surgery alone arm,[7-9] and shorter than that seen with sur1. ESPAC (European Study Group for gery plus chemoradiotherapy (13.9 months). These Pancreatic Cancer)-1 results are not consistent with the EORTC (EuropThe ESPAC (European Study Group for Pancreean Organisation for Research and Treatment of atic Cancer)-1 trial[2] raised concerns when pubCancer) trial of Klinkenbijl et.al.[9] The EORTC trial lished[3] regarding atypical statistical approaches, used a very similar chemoradiotherapy regimen

Both HIV- and EIAV-based lentiviral vectors mediate gene delivery to pancreatic cancer cells and human pancreatic primary patient xenografts.

Abstract: Few effective treatments for pancreatic cancer exist, especially for patients with advanced disease Gene therapy alone, or combined with current treatments, offers an alternative approach Here we examined the potential of primate and nonprimate lentivectors to mediate gene delivery to this cancer type VSV-G pseudotyped lentivectors based on human immunodeficiency type-1 virus (HIV-1) and equine infectious anemia virus (EIAV), containing the enhanced green fluorescent protein (EGFP) reporter gene were prepared and characterized for titer and RNA content Vector-mediated gene delivery was examined in five pancreatic cancer cell lines in vitro, and in MiaPaCa-2 cells as well as in five human primary patient biopsies xenografted subcutaneously in nude mice While individual cell lines showed differential sensitivities to transduction with lentivectors, all cell lines were successfully transduced with both vector types Similarly, both vectors transduced MiaPaCa-2 and all of the human primary patient xenografts We observed 6-29% transduction with HIV-based vectors (n=3 xenografts) and 18-30% with EIAV-based vectors (n=4 xenografts) Long-term EIAV-mediated gene expression was recorded in cell lines for up to 6 months We conclude that these vectors have potential as mediators of clinical gene therapy for pancreatic cancer treatment Moreover, they are useful laboratory research tools for pancreatic cancer research

Adjuvant chemotherapy—the standard after resection for pancreatic cancer

Abstract: Pancreatic cancer is one of the major causes of cancer death. Most patients present with advanced disease, and only 10% to 15% can undergo resection. Survival after curative surgery is poor, as recurrences occur either locally or in the liver. Adjuvant treatment has been employed to improve the poor prognosis. There is a clear-cut survival advantage with 5-fluorouracil (5-FU)/folinic acid or gemcitabine compared with observation, based on the results from the European Study Group for Pancreatic Cancer (ESPAC) 1 and Neuhaus studies. The survival advantage associated with chemotherapy is supported by an individual patient data meta-analysis. In contrast, there is no justification for the use of adjuvant chemoradiation based on the European Organization for Research and Treatment of Cancer (EORTC) and ESPAC-1 trial results. The use of chemoradiation followed by chemotherapy, as shown in the 1987 Gastrointestinal Tumor Study Group (GITSG) study and the recent Radiation Therapy Oncology Group (RTOG) 9704 combination study, has not proved to be superior to chemotherapy alone based on the results of the underpowered study. The standard of care for adjuvant therapy based on level I evidence is postoperative chemotherapy using 5-FU with folinic acid, providing a best estimate of 29% 5-year survival rate.

Pancreatic cancer — Adjuvant therapy

Abstract: Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%–15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation (with or without maintenance chemotherapy) has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level I evidence (from the ESPAC-1 trial) is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.